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1. 发明公开

EP2470212A1 METHOD OF TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE LEUKAEMIA 审中-公开
标题翻译：方法为费城染色体阳性白血病的治疗
公开(公告)号：EP2470212A1
公开(公告)日：2012-07-04
申请号：EP10819752.6
申请日：2010-10-01
申请人： CSL Limited , Hiwase, Devendra Keshaorao , Hughes, Timothy Peter , Lopez, Angel Francisco
发明人： HIWASE, Devendra, Keshaorao , HUGHES, Timothy, Peter , LOPEZ, Angel, Francisco , VAIRO, Gino, Luigi
IPC分类号： A61K39/395 , A61K31/4439 , A61K38/00 , A61K31/122 , A61K31/497 , A61P35/02
CPC分类号： C07K16/2866 , A61K31/122 , A61K31/4545 , A61K31/497 , A61K31/506 , A61K38/1793 , A61K38/193 , A61K38/202 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K47/642 , A61K47/6867 , C07K2317/24 , C07K2317/52 , C07K2317/732 , A61K2300/00
摘要： The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

2. 发明专利

AU2010302961A1 Method of treatment of philadelphia chromosome positive leukaemia 未知
公开(公告)号：AU2010302961A1
公开(公告)日：2012-04-19
申请号：AU2010302961
申请日：2010-10-01
申请人： CSL LTD , HIWASE DEVENDRA KESHAORAO , HUGHES TIMOTHY PETER , LOPEZ ANGEL FRANCISCO
发明人： HIWASE DEVENDRA KESHAORAO , HUGHES TIMOTHY PETER , LOPEZ ANGEL FRANCISCO , VAIRO GINO LUIGI
IPC分类号： A61K39/395 , A61K31/122 , A61K31/4439 , A61K31/497 , A61K38/00 , A61P35/02
摘要： The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

3. 发明专利

CA2775155A1 METHOD OF TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE LEUKEMIA 未知
公开(公告)号：CA2775155A1
公开(公告)日：2011-04-07
申请号：CA2775155
申请日：2010-10-01
申请人： CSL LTD , HIWASE DEVENDRA KESHAORAO , HUGHES TIMOTHY PETER , LOPEZ ANGEL FRANCISCO
发明人： VAIRO GINO LUIGI , HIWASE DEVENDRA KESHAORAO , HUGHES TIMOTHY PETER , LOPEZ ANGEL FRANCISCO
IPC分类号： A61K39/395 , A61K31/122 , A61K31/4439 , A61K31/497 , A61K38/00 , A61P35/02
摘要： The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

4. 发明申请

WO2010065433A1 METHOD OF OPTIMIZING THE TREATMENT OF PHILADELPHIA-POSITIVE LEUKEMIA WITH IMATINIB MESYLATE 审中-公开
标题翻译：利用肌醇六磷酸酯优化治疗菲律宾阳性淋巴细胞的方法
公开(公告)号：WO2010065433A1
公开(公告)日：2010-06-10
申请号：PCT/US2009/066045
申请日：2009-11-30
申请人： NOVARTIS AG , MEDVET SCIENCE PTY. LTD. , WANG, Yanfeng , KALEBIC, Thea , HUGHES, Timothy Peter , WHITE, Deborah
发明人： WANG, Yanfeng , KALEBIC, Thea , HUGHES, Timothy Peter , WHITE, Deborah
IPC分类号： A61K31/506 , A61K35/02
CPC分类号： A61K31/506
摘要： The present invention relates to a method of treating Philadelphia-positive leukemia (Ph+ leukemia), in a particular chronic myeloid leukemia (CML), in a human patient population. More specifically, the present invention pertains to a method of treating Ph+ leukemia, such as CML or Ph+ ALL, in a human patient suffering from Ph+ leukemia comprising the steps of (a) administering a predetermined fixed amount of Imatinib as a free base or in the form of a pharmaceutically acceptable salt thereof to the human patient, (b) collecting at least one blood sample from the patient, e.g. within the first 12 months of treatment, (c) determining the plasma trough level (Cmin) of Imatinib, (d) determining the OCT-1 Activity in the blood sample, and (e) adjusting the dose of Imatinib applied to the individual patient in a manner that an Imatinib Cmin value is achieved in the patient of at least 800 ng/mL, if in step (c) an Imatinib Cmin value of less than 800 ng/mL is found and in step (d) an OCT-1 Activity is found below 6.0 to 10.0 ng/200,000 cells..
摘要翻译：本发明涉及在人类患者群体中治疗特定慢性骨髓性白血病（CML）中的费城阳性白血病（Ph +白血病）的方法。更具体地，本发明涉及在患有Ph +白血病的人类患者中治疗Ph +白血病（例如CML或Ph + ALL）的方法，包括以下步骤：（a）施用预定的固定量的伊马替尼作为游离碱或其药学上可接受的盐的形式提供给人类患者，（b）从患者收集至少一种血液样品，在治疗的头12个月内，（c）确定伊马替尼的血浆谷值（Cmin），（d）确定血液样品中的OCT-1活性，和（e）调整施用于个体患者的伊马替尼剂量如果在步骤（c）中发现伊马替尼Cmin值小于800ng / mL，并且在步骤（d）中OCT-1 活动发现低于6.0至10.0ng / 20万个细胞。

5. 发明申请

WO2011022782A1 COMBINATIONS COMPRISING IMATINIB MESYLATE AND DICLOFENAC 审中-公开
标题翻译：包含甲基纤维素和DICLOFENAC的组合
公开(公告)号：WO2011022782A1
公开(公告)日：2011-03-03
申请号：PCT/AU2010/001109
申请日：2010-08-27
申请人： MEDVET SCIENCE PTY LTD , HUGHES, Timothy, Peter , WHITE, Deborah , D'ANDREA, Richard, James
发明人： HUGHES, Timothy, Peter , WHITE, Deborah , D'ANDREA, Richard, James
IPC分类号： A61K31/506 , A61K31/196 , A61P35/02
CPC分类号： A61K31/196 , A61K31/506 , A61K2300/00
摘要： The present invention relates to a method of treating Philadelphia-positive leukemia (Ph+ leukemia), especially chronic myeloid leukemia (CML), especially in human patients having low OCT-1 Activity ("low OA patients"), a combination comprising (a) imatinib or a pharmaceutically acceptable salt thereof and (b) diclofenac or a pharmaceutically acceptable salt thereof, the use of such combination for the manufacture of a medicament for the treatment of Ph+ leukemia and to a pharmaceutical composition comprising a quantity which is jointly therapeutically effective against a proliferative disease of a such combination.
摘要翻译：本发明涉及一种治疗费城阳性白血病（Ph +白血病），特别是慢性骨髓性白血病（CML）的方法，特别是在具有低OCT-1活性（“低OA患者”）的人类患者中，包括（a）伊马替尼或其药学上可接受的盐和（b）双氯芬酸或其药学上可接受的盐，使用这种组合来制备用于治疗Ph +白血病的药物和药物组合物，所述药物组合物包含联合治疗有效的量这种组合的增殖性疾病。

6. 发明申请

WO2009000023A1 METHOD FOR OPTIMIZING THE TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH ABL TYROSINE KINASE INHIBITORS 审中-公开
标题翻译：用ABL酪氨酸激酶抑制剂优化治疗慢性粒细胞白血病的方法
公开(公告)号：WO2009000023A1
公开(公告)日：2008-12-31
申请号：PCT/AU2008/000911
申请日：2008-06-20
申请人： MEDVET SCIENCE PTY LTD , HUGHES, Timothy Peter , WHITE, Deborah
发明人： HUGHES, Timothy Peter , WHITE, Deborah
IPC分类号： A61K31/506 , A61P35/02 , G01N33/60
CPC分类号： A61K31/506
摘要： The present invention relates to a method for evaluating patients to help optimizing the treatment of chronic myeloid leukemia (CML) in a human patient population. More specifically, the method comprises the steps of (a) determining the OCT-1 Activity in pre-therapy blood of a warm-blooded animal suffering from CML, and (b) administering a daily dose between about 500 and 1200 mg of Imatinib mesylate to the warm-blooded animal suffering from CML showing an OCT-1 Activity corresponding to Imatinib intracellular concentration below about 6.0 to 10.0 ng/200,000 cells, especially about 8.0 to 8.5 ng/200,000 cells.
摘要翻译：本发明涉及一种用于评估患者以帮助优化人类患者群体中慢性骨髓性白血病（CML）治疗的方法。更具体地，该方法包括以下步骤：（a）确定患有CML的温血动物的治疗前血液中的OCT-1活性，和（b）施用约500至1200mg的甲磺酸伊马替尼给患有CML的温血动物显示对应于伊马替尼细胞内浓度低于约6.0至10.0ng / 20万细胞，特别是约8.0至8.5ng / 20万细胞的OCT-1活性。

7. 发明申请

WO2006042362A1 USE OF 4-(4-METHYLPIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-(PYRIDIN-3-YL)PYRIMIDIN-2-YLAMINO)PHENYL]-BENZAMIDE TO INHIBIT THE TYROSINE KINASE RECEPTOR C-FMS 审中-公开
标题翻译：使用4-（4-甲基哌啶-1-基甲基）-N- [4-甲基-3-（4-（吡啶-3-基）嘧啶-2-基]氨基]苯基] - 苯甲酰胺抑制酪氨酸激酶受体C -fms
公开(公告)号：WO2006042362A1
公开(公告)日：2006-04-27
申请号：PCT/AU2005/001602
申请日：2005-10-17
申请人： MEDVET SCIENCE PTY LTD , DEWAR, Andrea, Louis , HUGHES, Timothy, Peter , LYONS, Alan, Bruce
发明人： DEWAR, Andrea, Louis , HUGHES, Timothy, Peter , LYONS, Alan, Bruce
IPC分类号： A61K31/506 , A61P25/28 , A61P35/00
CPC分类号： A61K31/506
摘要： This invention relates to the use of 4-(4-methylpiperazin-l-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2- ylamino)phenyl]-benzamide, (also known as imatinib, gleevec, glivec, cgp57148b or 8TI571), or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of c-fms associated diseases including; choriocarcinoma, malignant histiocytosis, embryonal carcinoma, endometrial carcinoma, brain microglial tumours, sarcoidosis, microglial cell involvement in normal and variant Creutzfeld- Jacob disease, and amyotrophic lateral sclerosis.
摘要翻译：本发明涉及4-（4-甲基哌嗪-1-基甲基）-N- [4-甲基-3-（4-吡啶-3-基）嘧啶-2-基氨基）苯基] - 苯甲酰胺（也称为伊马替尼，格列卫，glivec，cgp57148b或8TI571）或其药学上可接受的盐，用于制备用于治疗c-fms相关疾病的药物，包括：绒毛膜癌，恶性组织细胞增多症，胚胎癌，子宫内膜癌，脑小胶质细胞瘤，结节病，小胶质细胞参与正常和变异型克雅氏病，肌萎缩性侧索硬化。

8. 发明申请

WO2011038467A1 METHOD OF TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE LEUKAEMIA 审中-公开
标题翻译：治疗菲律宾染色体阳性白血病的方法
公开(公告)号：WO2011038467A1
公开(公告)日：2011-04-07
申请号：PCT/AU2010/001295
申请日：2010-10-01
申请人： CSL LIMITED , HIWASE, Devendra, Keshaorao , HUGHES, Timothy, Peter , LOPEZ, Angel, Francisco , VAIRO, Gino, Luigi
发明人： HIWASE, Devendra, Keshaorao , HUGHES, Timothy, Peter , LOPEZ, Angel, Francisco , VAIRO, Gino, Luigi
IPC分类号： A61K39/395 , A61K31/4439 , A61K38/00 , A61K31/122 , A61K31/497 , A61P35/02
CPC分类号： C07K16/2866 , A61K31/122 , A61K31/4545 , A61K31/497 , A61K31/506 , A61K38/1793 , A61K38/193 , A61K38/202 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K47/642 , A61K47/6867 , C07K2317/24 , C07K2317/52 , C07K2317/732 , A61K2300/00
摘要： The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.
摘要翻译：本发明提供了一种用于治疗患者中Ph +白血病的方法，包括给予患者（i）BCR-ABL酪氨酸激酶抑制剂，和（ii）选择性结合在Ph +白血病干细胞上表达的细胞表面受体的药剂。本发明进一步提供（i）和（ii）在治疗患者中Ph +白血病的药物中的用途或制造中的用途; 和包含（i）和（ii）的患者中用于治疗Ph +白血病的组合物。和包含（i）和（ii）的试剂盒。在一些实施方案中，酪氨酸激酶抑制剂是或不是伊马替尼; 吉西他滨，拉帕替尼，雷他替尼，奈替尼，semaxanib，舒尼替尼，toceranib，噻吩霉素，凡多他尼，瓦拉西尼，INNO-406，AP24534，XL228等组成的组，或者选自由dasatinib，尼罗替尼，bosutinib，axitinib，cediranib，crizotinib， PHA-739358，MK-0457，SGX393和DC2036; 或选自由达沙替尼和尼罗替尼组成的组。在一些实施方案中，所述试剂通过IL-3，G-CSF和GM-CSF中的至少一种与涉及信号传导的受体结合。在一些实施方案中，试剂是选自IL-3突变蛋白，G-CSF突变蛋白和GM-CSF突变蛋白的突变蛋白。在一些实施方案中，突变蛋白是IL-3突变蛋白。在一些实施方案中，所述试剂是能够结合IL-3的可溶性受体。

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